Equine infectious anemia virus (EIAV) is a member of the lentivirus subfamily of retroviruses. EIAV causes a unique disease characterized by repeated bouts of fever and viremia. Virus isolates recovered from sequential febrile episodes from the same animal can be distinguished serologically and biochemically, indicating that viral mutation plays a key role in persistence. Other features of EIAV infection include a short latent period prior to disease onset, the persistence of virus in the presence of competent host immune responses, and the eventual control of disease in many animals. Our long term goals are to understand the nature of EIAV persistence and pathogenesis as well as the dynamic interactions between virus and host that result in an episodic disease. The short latent period prior to disease onset makes EIAV a powerful tool for mutagenesis-based studies of pathogenesis as well as an ideal model in which to determine how viral mutation rates impact on the efficacy of vaccines and antiviral chemotherapies. The proposed studies focus on recovery of molecular clones of virulent EIAV strains and identification of those genetic elements that play key roles in tissue tropism and disease production. The specific aims of this proposal include: The recovery and characterization of virulent proviral clones of EIAV. Functional analysis of EIAV gene products and cis/acting sequences and their contributions to viral replication and disease. Determination of viral factors that influence cell tropism.